Disease Information: Tuberculosis (TB) is caused by a bacterium called Mycobacterium tuberculosis. The bacteria usually attacks the lungs, but can also attack any part of the body such as the kidney, spine, and brain. Tuberculosis can be spread through the air, just like a cold or the flu. It is contagious, but not easy to catch. Additionally, not everyone infected with TB bacteria becomes sick. As a result, two TB-related conditions exist: latent TB infection (LTBI) and TB disease. If not treated properly, TB disease can be fatal.
Essentiality: The glmU gene is essential in Mycobacterium tuberculosis, being required for optimal bacterial growth, and has been selected as a possible drug target for structural and functional investigation. GlmU is a bifunctional acetyltransferase/uridyltransferase that catalyses the formation of UDP-GlcNAc from GlcN-1-P. UDP-GlcNAc is a substrate for two important biosynthetic pathways: lipopolysaccharide and peptidoglycan synthesis.
UDP-N-acetyl-D-glucosamine (UDP-GlcNAc) is an essential precursor of peptidoglycan and the rhamnose-GlcNAc linker region of mycobacterial cell wall. In Mycobacterium tuberculosis H37Rv genome, Rv1018c shows strong homology to the GlmU protein involved in the formation of UDP-GlcNAc from other bacteria. GlmU is a bifunctional enzyme that catalyzes two sequential steps in UDP-GlcNAc biosynthesis. Glucosamine-1-phosphate acetyl transferase catalyzes the formation of N-acetylglucosamine-1-phosphate, and N-acetylglucosamine-1-phosphate uridylyltransferase catalyzes the formation of UDP-GlcNAc. Since inhibition of peptidoglycan synthesis often results in cell lysis, M. tuberculosis GlmU is a potential anti-tuberculosis (TB) drug target.
NCBI # : 886069
Protein ID: NP_215534
Organism: Mycobacterium Tuberculosis
Etiologic Risk Group (see link below): Group 3
http://www.bacterio.net/-hazard.html#group3
Disease Information:
Tuberculosis (TB) is caused by a bacterium called Mycobacterium tuberculosis. The bacteria usually attacks the lungs, but can also attack any part of the body such as the kidney, spine, and brain. Tuberculosis can be spread through the air, just like a cold or the flu. It is contagious, but not easy to catch. Additionally, not everyone infected with TB bacteria becomes sick. As a result, two TB-related conditions exist: latent TB infection (LTBI) and TB disease. If not treated properly, TB disease can be fatal.
https://www.cdc.gov/tb/topic/basics/default.htm
https://www.webmd.com/lung/understanding-tuberculosis-basics#1
Link to TDR targets page:
http://tdrtargets.org/targets/view?gene_id=6147
Link to Gene Database page (NCBI):
https://www.ncbi.nlm.nih.gov/gene/886069
https://www.uniprot.org/uniprot/P9WMN3
Essentiality:
The glmU gene is essential in Mycobacterium tuberculosis, being required for optimal bacterial growth, and has been selected as a possible drug target for structural and functional investigation. GlmU is a bifunctional acetyltransferase/uridyltransferase that catalyses the formation of UDP-GlcNAc from GlcN-1-P. UDP-GlcNAc is a substrate for two important biosynthetic pathways: lipopolysaccharide and peptidoglycan synthesis.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2651758/
UDP-N-acetyl-D-glucosamine (UDP-GlcNAc) is an essential precursor of peptidoglycan and the rhamnose-GlcNAc linker region of mycobacterial cell wall. In Mycobacterium tuberculosis H37Rv genome, Rv1018c shows strong homology to the GlmU protein involved in the formation of UDP-GlcNAc from other bacteria. GlmU is a bifunctional enzyme that catalyzes two sequential steps in UDP-GlcNAc biosynthesis. Glucosamine-1-phosphate acetyl transferase catalyzes the formation of N-acetylglucosamine-1-phosphate, and N-acetylglucosamine-1-phosphate uridylyltransferase catalyzes the formation of UDP-GlcNAc. Since inhibition of peptidoglycan synthesis often results in cell lysis, M. tuberculosis GlmU is a potential anti-tuberculosis (TB) drug target.
https://www.ncbi.nlm.nih.gov/pubmed/18573680/
Is it a monomer or multimer as a biological unit? make prediction at http://www.ebi.ac.uk/msd-srv/prot_int/pistart.html): multimer
Druggable Target (list number or cite evidence from a paper/database showing druggability in another organism): 0.2
http://tdrtargets.org/targets/view?gene_id=6147
https://www.sciencedirect.com/science/article/pii/S1472979215300159?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/18573680/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3695056/#R84
E.C# : 2.3.1.157
Link to BRENDA EC# page:
http://www.brenda-enzymes.org/enzyme.php?ecno=2.3.1.157&Suchword=2.3.1.157&reference=&UniProtAcc=&organism%5B%5D=Mycobacterium+tuberculosis&show_tm=0
Enzyme Assay Information:
https://www.ncbi.nlm.nih.gov/pubmed/18573680
http://aac.asm.org/content/53/6/2306.long
Links to assay reagents (substrates) pages:
http://www.profoldin.com/glmu-assay.html
E.coli GlmU Assay Kit Plus-100
Catalong No. GLU100KE
Price: $395.00
Structure (PDB or Homology model):
2QKX
3D8V
3D98
3DJ4
3FOQ
3ST8
4G3Q
4G3S
4G87
4HCQ
Current Inhibitors:
https://www.brenda-enzymes.org/all_enzymes.php?ecno=2.3.1.157&table=Inhibitors#TAB
Expression Information (has it been expressed in bacterial cells): Yes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2531282/
Purification Method: Hanging-drop vapour-diffusion method
https://www.researchgate.net/publication/23232128_Expression_purification_and_preliminary_crystallographic_analysis_of_N_-acetylglucosamine-1-phosphate_uridylyltransferase_from_Mycobacterium_tuberculosis
Image of protein (PyMol with features delineated and shown separately):
Amino Acid Sequence:
Length of your protein in Amino Acids: 495 AA
Molecular Weight of your protein in kiloDaltons using the Expasy ProtParam website: 51583.99 kDa
Molar Extinction coefficient of your protein at 280 nm wavelength: 24535
TMpred graph Image(http://www.ch.embnet.org/software/TMPRED_form.html). Input your amino acid sequence to it.
CDS Gene Sequence:
GC Content: 67.47%